No abstract

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding.

Extraocular sebaceous carcinoma is an uncommon neoplasm usually localized on the head and neck. We report a case of sebaceous carcinoma of the axillary skin with a highly aggressive behavior. The patient was a 43-year-old black man who developed multiple cutaneous and lymph node metastases shortly after the excision of primary sebaceous carcinoma of the axillary skin. Many neoplastic aggregations were identified within the lumina of the dermal lymphatic vessels in the excised specimen of the primary neoplasm. Although extraocular sebaceous carcinoma has been traditionally considered a less aggressive neoplasm than its ocular counterpart, a review of the literature and this case demonstrate that extraocular sebaceous carcinoma may also lead to disseminated metastatic disease.

One hundred thirty-eight Nigerian patients with pityriasis rosea were studied. Patients with the condition constituting 2.4% of all patients seen in two skin clinics in Northern Nigeria in a period of over three years. The proportional rate of pityriasis rosea parallels figures from other African studies, and is higher than values obtained in European series. Pyriasis rosea in Nigerians appears to be more florid and has a greater tendency to overstep the classic boundaries of distribution on the body, to affect the face and involve the oral cavity. The sex and age distribution was similar to European series, although some lowering of the age of onset of the condition was observed. No relationship between the frequency of pityriasis rosea and season was found.